The neural crest is unique to vertebrates and has allowed the evolution of their complicated craniofacial structures. During vertebrate evolution, the acquisition of the neural crest must have been accompanied by the emergence of a new gene regulatory network (GRN). Here, to investigate the role of protein evolution in the emergence of the neural crest GRN, we examined the neural crest cell (NCC) differentiation-inducing activity of chordate FoxD genes. Amphioxus and vertebrate (Xenopus) FoxD proteins both exhibited transcriptional repressor activity in Gal4 transactivation assays and bound to similar DNA sequences in vitro. However, whereas vertebrate FoxD3 genes induced the differentiation of ectopic NCCs when overexpressed in chick neural tube, neither amphioxus FoxD nor any other vertebrate FoxD paralogs exhibited this activity. Experiments using chimeric proteins showed that the N-terminal portion of the vertebrate FoxD3 protein is critical to its NCC differentiation-inducing activity. Furthermore, replacement of the N-terminus of amphioxus FoxD with a 39-amino-acid segment from zebrafish FoxD3 conferred neural crest-inducing activity on amphioxus FoxD or zebrafish FoxD1. Therefore, fixation of this N-terminal amino acid sequence may have been crucial in the evolutionary recruitment of FoxD3 to the vertebrate neural crest GRN.

• Klíčová slova
• Amphioxus, FoxD3, Neural crest,
• MeSH
• crista neuralis fyziologie   MeSH
• forkhead transkripční faktory chemie   genetika   fyziologie   MeSH
• genetická transkripce MeSH
• klonování DNA MeSH
• obratlovci embryologie   MeSH
• represorové proteiny fyziologie   MeSH
• vývojová regulace genové exprese * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• forkhead transkripční faktory MeSH
• represorové proteiny MeSH

BACKGROUND: TALE-class homeodomain transcription factors Meis and Pbx play important roles in formation of the embryonic brain, eye, heart, cartilage or hematopoiesis. Loss-of-function studies of Pbx1, 2 and 3 and Meis1 documented specific functions in embryogenesis, however, functional studies of Meis2 in mouse are still missing. We have generated a conditional allele of Meis2 in mice and shown that systemic inactivation of the Meis2 gene results in lethality by the embryonic day 14 that is accompanied with hemorrhaging. RESULTS: We show that neural crest cells express Meis2 and Meis2-defficient embryos display defects in tissues that are derived from the neural crest, such as an abnormal heart outflow tract with the persistent truncus arteriosus and abnormal cranial nerves. The importance of Meis2 for neural crest cells is further confirmed by means of conditional inactivation of Meis2 using crest-specific AP2α-IRES-Cre mouse. Conditional mutants display perturbed development of the craniofacial skeleton with severe anomalies in cranial bones and cartilages, heart and cranial nerve abnormalities. CONCLUSIONS: Meis2-null mice are embryonic lethal. Our results reveal a critical role of Meis2 during cranial and cardiac neural crest cells development in mouse.

• MeSH
• chrupavka abnormality   embryologie   MeSH
• crista neuralis embryologie   metabolismus   MeSH
• forkhead transkripční faktory biosyntéza   genetika   MeSH
• hlavové nervy embryologie   MeSH
• homeodoménové proteiny genetika   MeSH
• krvácení genetika   MeSH
• lebka embryologie   inervace   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• represorové proteiny biosyntéza   genetika   MeSH
• srdce embryologie   MeSH
• transkripční faktor SOX9 biosyntéza   genetika   MeSH
• vrozené srdeční vady embryologie   genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• forkhead transkripční faktory MeSH
• Foxd3 protein, mouse MeSH Prohlížeč
• homeodoménové proteiny MeSH
• Mrg1 protein, mouse MeSH Prohlížeč
• represorové proteiny MeSH
• Sox9 protein, mouse MeSH Prohlížeč
• transkripční faktor SOX9 MeSH